000165688 001__ 165688
000165688 005__ 20260113234334.0
000165688 0247_ $$2doi$$a10.1161/ATVBAHA.108.183384
000165688 0248_ $$2sideral$$a66559
000165688 037__ $$aART-2009-66559
000165688 041__ $$aeng
000165688 100__ $$aVilla-Bellosta, R.$$uUniversidad de Zaragoza
000165688 245__ $$aPhosphonoformic Acid Prevents Vascular Smooth Muscle Cell Calcification by Inhibiting Calcium-Phosphate Deposition
000165688 260__ $$c2009
000165688 5060_ $$aAccess copy available to the general public$$fUnrestricted
000165688 5203_ $$aObjective— The role of inorganic phosphate in the pathogenesis of vascular calcification (VC) has been studied extensively in recent years. Phosphonoformic acid (PFA), an inhibitor of type II Pi transporters, has been traditionally used to study the involvement of Pi transport in VC, because PFA also prevents calcium deposition in vitro. However, aortic vascular smooth muscle cells (VSMCs) only express PFA-resistant, type III transporters (Pit-1 and Pit-2). Therefore, in this article we have studied the mechanism of VC prevention by PFA.
Methods and Results— Radiotracer Pi uptake in rat VSMCs was not inhibited at the concentrations at which PFA prevents calcification. Alternative mechanisms whereby PFA could prevent calcification, such as cytotoxicity or phosphodiesterase inhibition, have also been excluded. The progression of calcification also took place in fixed cells. The kinetics of VC prevention by PFA, pyrophosphate, phosphonoacetate, and bisphosphonates was similar in live and fixed cells, showing mean effective concentrations in the micromolar range.
Conclusions— PFA mainly prevents VC through a physicochemical mechanism that is independent of any cellular metabolic activity, including Pi transport. Conversely, PFA seems to act similarly to its chemical analogues, inorganic pyrophosphate, and bisphosphonates, as suggested decades ago.
000165688 536__ $$9info:eu-repo/grantAgreement/ES/MEC/BFU2016-06284-BFI
000165688 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000165688 590__ $$a7.235$$b2009
000165688 591__ $$aPERIPHERAL VASCULAR DISEASE$$b3 / 61 = 0.049$$c2009$$dQ1$$eT1
000165688 591__ $$aHEMATOLOGY$$b6 / 61 = 0.098$$c2009$$dQ1$$eT1
000165688 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000165688 700__ $$0(orcid)0000-0003-3457-323X$$aSorribas, V.$$uUniversidad de Zaragoza
000165688 7102_ $$11000$$2807$$aUniversidad de Zaragoza$$bDpto. Anat.Pat.Med.Leg.For.To.$$cArea Toxicología
000165688 773__ $$g29, 5 (2009), 761-766$$pArterioscler. thromb. vasc. biol.$$tArteriosclerosis, Thrombosis, and Vascular Biology$$x1079-5642
000165688 8564_ $$s2753672$$uhttps://zaguan.unizar.es/record/165688/files/texto_completo.pdf$$yPostprint
000165688 8564_ $$s672464$$uhttps://zaguan.unizar.es/record/165688/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000165688 909CO $$ooai:zaguan.unizar.es:165688$$particulos$$pdriver
000165688 951__ $$a2026-01-13-22:05:58
000165688 980__ $$aARTICLE